The present invention relates to individualized porous particles having a volume-average diameter of 10 μm or less and containing at least one cosmetically or pharmaceutically active compound. The present invention further relates to use of such particles for transporting and releasing an active compound in the pilosebaceous unit.
To increase the efficacy of formulations for topical application, whether they are cosmetic or pharmaceutical in type, certain methods have already been proposed that aim to improve penetration of active molecules into the stratum corneum forming the superficial layer of skin. By way of example, mention may be made of methods using, as vehicles for active molecules, liposomes, nanocapsules, O/W emulsions, short alcohols, glycols, etc.
The pilosebaceous unit forms, within the stratum corneum, the epidermis, the dermis and an invagination comprising a hair follicle and a sebaceous gland. The pilosebaceous unit is a site of considerable biological and enzymatic activity which has a major effect on the appearance of the skin. Among these effects, mention may be made, for example, of the influence of the production of the sebum on the greasy or dry nature of the skin, and the influence of the growth or loss of growth of body hair or head hair on the pilosity of the skin. The pilosebaceous unit can also be the subject of an inflammatory process. Such a process can have various causes and can in particular be related to the presence of microorganisms. This process can result in or contribute to the manifestation of a certain number of skin conditions such as acne. In addition, the pilosebaceous unit constitutes a potential route of passage for agents intended to act on deep skin tissues, such as, for example, agents of the deep anti-wrinkle type, the slimming type, etc.
The structure of this pilosebaceous unit, both by virtue of its morphology with the presence of hair, and by virtue of its physiology with a continuous flow of sebum, naturally opposes the penetration and/or the diffusion of active compounds within and into the depths of the pilosebaceous unit.
However, methods for targeting active compounds into the pilosebaceous unit have already been proposed.
EP 0 375 520 describes the use of microspheres of natural or synthetic polymers or of fatty substances with a melting point above 50° C., loaded at least with an active product, and in which at least 80% by weight of the microspheres are between 3 μm and 10 μm in diameter, for preferentially transporting the active product into the pilosebaceous unit. The microspheres described in that application are either microspheres consisting of crosslinked materials, or solid microspheres loaded by partial solubilization of their constituent materials, and which have a specific surface area of less than 1 m2/g. In addition, the processes for preparing microspheres described in EP 0 375 520, which comprise the encapsulation of the active compound either by means of solvents having sufficient affinity with respect to the material making up the microsphere, or by an “emulsification-evaporation” method, only allow approximate control of the homogeneity of the microspheres obtained. As a result, the microspheres have a low or varied capacity to load the active compound and a low or varied capacity to release the active compound in the pilosebaceous unit.
WO 02/07674 proposes a method for increasing the penetration of an active compound into the pilosebaceous unit using a composition in the form of microspheres or liposomes having the property of being introduced into the follicle and of swelling therein by virtue of subsequently being in contact with a swelling agent, so as to generate a passage into the follicle. However, WO 02/07674 does not provide any concrete example illustrating the proposed method and does not therefore make it possible to verify the effectiveness of the proposed method.
U.S. Pat. No. 6,287,549 describes a method of hair removal using a composition comprising organic microparticles loaded with chromophore agents, in which at least 80% by weight of the microparticles are between 3 and 10 μm in size, in order to transport the chromophore agent into the pilosebaceous unit. These microparticles may be of various types and may be loaded with chromophores either as they are formed, or by impregnation of already formed microcapsules. In these microparticles, the compounds transported are not active compounds as such, since they require the intervention of an outside factor in order to be able to exercise an effect. In addition, exercising of this effect does not require their release from the microparticles. Moreover, U.S. Pat. No. 6,287,549, which explicitly provides for an optional step of application of a composition for solubilizing the chromophores so as to allow their release from the microparticles, does not suggest the possibility of a passive release and even teaches away from such passive release.
U.S. Pat. No. 4,690,825 describes vehicles consisting of porous particles which are between 10 μm and 100 μm in size, for the controlled release of active ingredients. These particles are prepared by copolymerization of monomers based on styrene, vinyl stearate and divinylbenzene or methyl methacrylate and ethylene glycol dimethyl methacrylate, in the presence of a porogen which is also the active ingredient. There is a risk that products so prepared will contain residues from preparation, which are likely to affect the products' innocuousness.
WO 99/53904 describes soft capsules containing an oily suspension or a silicone/polyethylene glycol emulsion and spherical porous microparticles prepared in particular according to U.S. Pat. No. 4,690,825, mentioned above. More precisely, this application describes porous microparticles having a mean particle diameter by weight of 20 μm, loaded either with retinol or with ascorbic acid.
U.S. Pat. No. 6,387,995 describes a process for producing an adsorbent polymer in the form of agglomerated, i.e., non-individualized, microparticles with a very low density ranging from 0.02 g/cm3 to 0.1 g/cm3, capable of trapping lipophilic compounds. The amount of compound trapped in the particles is negligible compared with that of the compound trapped in the space formed by the agglomerated particles.